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Cited by 93Cell death mechanisms and regulationInflammasome and immune disordersFerroptosis and cancer prognosis

Apoptin induces pyroptosis of colorectal cancer cells via the GSDME-dependent pathway

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Liu, Zirui, Li, Yiquan, Zhu, Yilong, Li, Nan, Li, Wenjie, Shang, Chao, Song, Gaojie, Li, Shanzhi +10 more·2022·International Journal of Biological Sciences
DOI 10.7150/ijbs.64350PMC PMC8741846
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Abstract

Apoptin is a small molecular weight protein encoded by the VP3 gene of chicken anemia virus (CAV).It can induce apoptosis of tumor cells and play anti-tumorigenic functions.In this study, we identified a time-dependent inhibitory role of apoptin on the viability of HCT116 cells.We also demonstrated that apoptin induces pyroptosis through cleaved caspase 3, and with a concomitant cleavage of gasdermin E (GSDME) rather than GSDMD.GSDME knockdown switched the apoptin-induced cell death from pyroptosis to apoptosis in vitro.Furthermore, we demonstrated that the effect of apoptin on GSDME-dependent pyroptosis could be mitigated by caspase-3 and caspase-9 siRNA knockdown.Additionally, apoptin enhanced the intracellular reactive oxygen species (ROS), causing aggregation of the mitochondrial membrane protein Tom20.Moreover, bax and cytochrome c were released to the activating caspase-9, eventually triggering pyroptosis.Therefore, GSDME mediates the apoptin-induced pyroptosis through the mitochondrial apoptotic pathway.Finally, using nude mice xenografted with HCT116 cells, we found that apoptin induces pyroptosis and significantly inhibits tumor growth.Based on this mechanism, apoptin may provide a new strategy for colorectal cancer therapy.

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  • MGF has been shown to promote the caspase cascade through multiple upstream regulators, including the Bcl-2 protein family and cytochrome c-mediated pathways.

    “MGF has been shown to promote this cascade through multiple upstream regulators, including the Bcl-2 protein family and cytochrome c-mediated pathways (60).”

    From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [60]

    The Results and Discussion describe apoptin acting through Bax, cytochrome C and caspases in colorectal cancer cells, not MGF. Searches for “MGF” and “mangiferin” found no passage addressing whether MGF promotes this cascade. (LLM, conf=0.78)

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Research works printed but not linked: 41

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Cited by

Sorted by citations

Authors
Liu, Z., Li, Y., Zhu, Y., Li, N., Li, W., Shang, C., Song, G., Li, S., Cong, J., Li, T., Xiu, Z., Lu, J., Ge, C., Yang, X., Li, Y., Sun, L., Li, X., & Jin, N.
Affiliations
  • Jilin University (CN)
  • Changchun University of Chinese Medicine (CN)
  • Chinese Academy of Agricultural Sciences (CN)
  • Jilin Province Tumor Hospital (CN)
Corresponding author
Jin, Ningyi
ORCID
Venue
International Journal of Biological Sciences
Publisher
Ivyspring International Publisher
Published
2022
Volume
18
Issue
2
Pages
717-730
ISSN
1449-2288 (ISSN-L)
DOI
10.7150/ijbs.64350
PMC
PMC8741846
OpenAlex
W4200114539
Cited by
93
References
2
Citations by year
2026: 10 · 2025: 20 · 2024: 21 · 2023: 28 · 2022: 14
FWCI
5.26
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • International Journal of Biological Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
People's Government of Jilin Province
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
Keywords
apoptin, pyroptosis, colorectal cancer, gasdermin E, gasdermin D, caspase-3, caspase-9, reactive oxygen species, mitochondrial apoptosis, Tom20, Bax, cytochrome c, HCT116 cells, chicken anemia virus, tumor growth inhibition
MeSH terms
Pyroptosis, Gasdermins, Animals, Female, Humans, Mice, Inbred BALB C, Mice, Nude, Mitochondria, Colorectal Neoplasms, Reactive Oxygen Species, Xenograft Model Antitumor Assays, Cytochromes c, HCT116 Cells, bcl-2-Associated X Protein, Mice, Pore Forming Cytotoxic Proteins, Caspase 3, Caspase 9

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